AbstractStudies on the role of human interleukin (IL)‐5 in B cell growth and differentiation have yielded conflicting results. To clarify this issue, we studied the role of purified recombinant IL‐5 on activated human B cells which were depleted of Tcells and adherent cells. Human IL‐5 augments IgM secretion, but not IgG or IgA secretion of purified human B cells activated with staphylococcal A Cowan 1 strain (SAC). However, the period of B cell activation with SAC is critical for the B cell to respond to IL‐5. After 24 h of SAC activation, human B cells are responsive to the IL‐5 signal, but with longer periods of activation, IL‐5 responsiveness diminishes. This may explain some of the previous conflicting results. The IgM enhancement was not seen when B cells were activated with pokeweed mitogen. In addition, human recombinant IL‐4 synergized with IL‐5 in augmenting IgM secretion by SAC‐activated B cells, while IL‐5 synergized with IL‐2 to augment IgM, IgG and IgA secretion by SAC‐activated B cells. As the purified IL‐5 was derived from a COS‐1 cell supernatant, and COS‐1 cells secrete IL‐6, we examined whether a polyclonal IL‐6 antibody blocked the IgM‐enhancing activity of IL‐5. IL‐6 antibody did not block the IL‐5 enhancement of IgM secretion, but a monoclonal antibody to IL‐5 inhibited the human IL‐5 activity on human B cells. These results demonstrate that human IL‐5 augments IgM secretion of SAC‐activated human B‐cells. In addition, this lymphokine synergizes with IL‐4 and IL‐2 in supporting Ig secretion.